According to the CDC, about 1.2 million people in the U.S. have HIV, the virus that causes AIDS; there are approximately 50,000 new HIV infections each year. Worryingly, 20 percent of HIV-infected people are not even aware that they are infected (26% in Canada). And one-third of those with a new HIV diagnoses progressed to AIDS within 12 months. So there is a strong public health incentive to identifying patients earlier so that they are less likely to transmit the infection to others, and so that they receive earlier treatment.

The long path of HIV testing

Testing has been limited to medical settings—first to hospitals (1980s), where a requirement was pre- and post- test counseling of the patient.

In 2002, FDA approved the first CLIA-waived rapid HIV test, which allowed for testing to be done in mobile outreach centers. The FDA looked at a staged approaches to achieving the goal of a home-use test, looking not only at test accuracy, but at test interpretation, and willingness of test subjects to medical follow-up. The first phase looked at test sensitivity and specificity when the test was run by trained personnel. This culminated in the 2004 approval of the OraQuick ADVANCE Rapid HIV-1/2 antibody test on oral fluid. This test showed a 99.3 percent sensitivity and 99.8 percent specificity.

The second phase looked at sensitivity and specificity of untrained users under observation, in 2008. In the Phase 2B Observed use trial, there were 2% of operational errors observed. These errors prevented users from obtaining an HIV test result; revisions were then made to the packaging and labeling instructions. When those results looked promising, with a sensitivity of 97.9% and specificity of 99.79%, the third phase extended testing to the intended-use setting.

Reviewing the Orasure background materials to the FDA and the staged testing details, I’m impressed with the care and level of detail that went into this product’s development—including not only the actual testing, but tests of label understanding, revisions, and creation of the call center.

Risks and down-sides of HIV home testing

The FDA itself notes a number of negatives: “The potential risks of an HIV home-use test include not fully comprehending the limitations of a screening test, such as misunderstanding a negative result when testing during the window period or the incomplete understanding of a false positive result. Home-use tests lack live counseling, resulting in the potential for adverse outcomes if the user obtains an unexpected result without concurrent live counseling.

Additional risks include the inability to reach individuals for medical follow-up, partner notification, and public health reporting. There is also the potential for coercive testing and testing by unprepared minors."

One critical decision will be the price point that OraSure sets for their test. Currently priced at $17.50 for clinics, estimates are in the $40-60 range. While that will be good for investors, it’s not so good for patients. In surveys, 46% said they would pay no more than $20 for a test; 13% said they would only take the test if it were free. And undoubtedly many who would benefit from an OTC test will be unable to pay that much several times a year, which is the recommended interval for some high-risk groups. So from a public health perspective, the pricing will be critical as to the test’s impact.

Because this new test can be done in private, at home, it is hoped that more people will be tested. Importantly, 41% of Phase 3 study participants found to be HIV positive reported they had never before been tested; many indicated they would not have been tested without the OTC self-testing option. Projections are that in a million tests, 9,087 additional HIV positive individuals would be identified, who would have been missed by traditional testing methods.

I’m concerned about the relatively low sensitivity, but looking at projections, the approval now makes more sense from a public health perspective. It comes down to the risk/benefit for the individual vs. the community as a whole. For the individual who receives the 1/12 false negative result, the test has the potential to be quite harmful. They might indulge in riskier behaviors and put their partners at additional risk. But for the ~9,000/million who are identified as HIV positive, and for their partners, this test is extraordinarily beneficial, enabling earlier treatment. The test is also projected to prevent 700 additional HIV transmissions per million people. So the FDA concluded that if just 1% of Americans uses the test, OraQuick could identify up to 45,000 previously undetected HIV-positive people and prevent around 4,000 new infections each year. I wonder if anyone has calculated yet the breakpoint where providing the test for free (or perhaps on a sliding scale) would be a cost-effective strategy. I hope OraQuick will be priced to have the greatest public health impact.

The views expressed are those of the author(s) and are not necessarily those of Scientific American.

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ABOUT THE AUTHOR(S)

Judy Stone

Judy Stone, MD is an infectious disease specialist, experienced in conducting clinical research. She is the author of Conducting Clinical Research, the essential guide to the topic. She survived 25 years in solo practice in rural Cumberland, Maryland, and is now broadening her horizons. She particularly loves writing about ethical issues, and tilting at windmills in her advocacy for social justice. As part of her overall desire to save the world when she grows up, she has become especially interested in neglected tropical diseases. When not slaving over hot patients, she can be found playing with photography, friends' dogs, or in her garden. Follow on Twitter @drjudystone or on her website.

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